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What is erythropoietin?
Erythropoietin (also known as EPO) is a growth factor that stimulates the production of red blood cells. Most of the cells in the blood are red blood cells, whose main function is to carry oxygen throughout the body.
Erythropoietin is used to treat anemia resulting from kidney failure or cancer treatment. It is considered to be an alternative to blood transfusions.
There are several different types of erythropoietins. Procrit® and Epogen® are two brands of epoetin alfa. Aranesp® (darbepoetin alfa) is another type of erythropoietin. The major difference between Procrit/Epogen and Aranesp is that Aranesp is given less often than Procrit. Otherwise, all three agents work equally well in the treatment of anemia.
How is anemia treated in multiple myeloma?
Anemia is typically defined as having a hemoglobin (Hb) level below normal. Hemoglobin is the substance found within red blood cells that carries oxygen from the lungs to the tissues in the body. Normal hemoglobin levels are:
•12 to 16 g/dL for women
•14 to 18 g/dL for men
Severity of Anemia Hemoglobin Level (g/dL)
•Mild (10 or more)
•Life-Threatening (Less than 6.5)
Treatment of anemia in patients with myeloma is complex, because both the disease itself and the treatments for myeloma may cause anemia. For this reason, a step-wise approach is recommended:
•Treatment with myeloma drugs to control the underlying cancer. Patients who respond to myeloma treatment, especially those who achieve a complete remission, may have an improvement in their anemia.
•Check and treat other causes of anemia such as low levels of iron or other nutrients (folate, vitamin B12), internal bleeding or kidney problems.
•If anemia is still moderate (but causing symptoms) or severe then blood transfusions or erythropoietin therapy should be used.
Erythropoietin is an alternative to blood transfusions in patients with moderate to severe anemia, resulting from their myeloma treatment. If anemia is severe and requires immediate treatment, patients should receive a blood transfusion. A blood transfusion may also be necessary in cases where a patient does not respond to erythropoietin therapy.
In some cases, erythropoietin therapy may also be considered for mild anemia (Hb = 10-11 g/dL), such as:
•Elderly patients with heart and lung problems
•Patients with arthrosclerosis
•Patients who have angina or chest pains
Significant symptoms impacting patient’s quality of life such as: substantially reduced ability to take care of themselves, reduced energy and ability to exercise (e.g., walking, climbing stairs).
Treating anemia allows more oxygen to circulate throughout the body, which can result in more energy, reduced fatigue, and the restored ability to be active. Several clinical trials have shown that treating anemia associated with cancer treatment with erythropoietin:
Significantly improved quality of life, including the ability to perform usual daily activities and to work. Reduced the need for transfusions in patients receiving chemotherapy by about half. May reduce the number of days cancer patients with anemia spend in the hospital.
What are the possible side effects?
Erythropoietic agents are generally well tolerated. However, recent studies have shown that these drugs have been associated with an increased risk of blood clots. Factors that can increase the risk of developing blood clots include:
•A history of blood clots
•Prolonged periods of bed rest or limited activity
•Treatment with some common myeloma drugs including Revlimid, Thalomid, dexamethasone, Adriamycin and Doxil.
Preventive treatment with a blood thinner (such as heparin) may be considered for high-risk patients.
Erythropoietin Safety Concern: Do erythropoietins decrease cancer survival?
A number of studies in several types of cancers have shown that patients taking erythropoietin did not live as long as other patients. Most of these studies were not conducted in multiple myeloma. Further, erythropoietin was used in a way that is different from how it is typically used in practice today. In contrast, an analysis of studies where erythropoietin was used appropriately did not show any impact on survival.
Due to these possible safety problems, erythropoietin drugs are now used more cautiously.
You and your doctor will discuss the benefits and risks of erythropoietin therapy in your individual case.
How are erythropoietin drugs given?
Erythropoietin therapy is given as an injection under the skin at home by patients or caregivers.
The most common initial dosing schedules for the various types of erythropoietins are listed below:
•Procrit/Epogen: 150 units/kg three times a week or 40,000 units/kg once weekly
•Aranesp: 2.25mcg/kg once a week or 500mcg every three 3 weeks
Your dose may be changed based upon how you respond to therapy. In addition, depending on your individual situation, your doctor may recommend an alternate dosing schedule.
Supplemental iron may be given in addition to erythropoietin therapy.
How is the effectiveness of erythropoietin determined?
Blood tests are used to monitor erythropoietin therapy. The effectiveness of therapy is measured by the increase in hemoglobin and a related test called hematocrit (the number and size of red blood cells) following therapy.
It takes some time for the body to produce new blood cells, so the effect of erythropoietic agents may not be seen for 2 to 6 weeks. The amount of time it takes, and the dose needed varies from patient to patient.
Overall, about 60% to 70% of cancer patients receiving cancer treatment respond to erythropoietic agents. An early hemoglobin response to therapy (≥1 g/dL rise after 4 weeks of therapy) in patients with treatment-related anemia is often associated with reduced transfusion requirements, higher hemoglobin response rates, and improved quality of life. Having adequate iron levels may also improve responses to erythropoietin therapy.
Patients less likely to respond to erythropoietic therapy include those with reduced bone marrow function at the start of erythropoietic treatment, those with heavy transfusion needs as well as patients with persistent infections.
How are erythropoietin drugs used with high dose chemotherapy and autologous stem cell transplant?
Anemia is a common side effect of high-dose chemotherapy and autologous stem cell transplant due to the chemotherapy’s effect on the blood-producing cells in the bone marrow. Administration of erythropoietin immediately after transplant has been less effective in treating this type of anemia. However, with increasing time, erythropoietin re-gains its effectiveness.
Erythropoietin EPO drug side effects, health benefits, danger, risks by Ray Sahelian, M.D.
Feb 27 2014Erythropoietin is a hypoxia-induced hormone that is a major regulator of normal erythropoiesis. Over the last decade, the production of recombinant human erythropoietin has revolutionized the treatment of anemia associated with chronic renal failure, and has led to a greater understanding of anemia pathophysiology and to the elucidation of the interactions of erythropoietin, iron, and erythropoiesis.
Potential survival benefits associated with correction of anemia have expanded considerably the indications of erythropoietin use in various patient populations and are leading to consideration of earlier, more aggressive treatment of moderate anemia. The results of such treatment are promising in a variety of new clinical settings, including anemia associated with congestive heart failure. Furthermore, the erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes and preclinical studies have established erythropoietin to be a pleiotropic cytokine with anti-apoptotic activity and tissue-protective actions in the cardiovascular system, beyond correction of hemoglobin levels. However, one should be cautious about being overly excited about these possibilities until more studies are done. See below for potential side effects and risks.
Clin Exp Nephrol. Feb 4 2014. Effect of a combined treatment with erythropoietin and melatonin on renal ischemia reperfusion injury in male rats. EPO and melatonin combination treatment exerted more nephroprotective effects than EPO treatment and nearly had protective effects similar to MEL treatment.
Erythropoietin side effects, danger, risks, caution
Despite some potential adverse effects, such as hypertension, and the occurrence of erythropoietin resistance, early studies in mild heart failure patients with anemia suggest that erythropoietin therapy is effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Achieving higher target hemoglobin levels with erythropoietic agents in patients with renal insufficiency is associated with a significantly higher risk of serious and life-threatening cardiovascular complications. Dr. Dawn L. Hershman, of Columbia University Medical Center, New York City, identified 56,210 patients aged 65 and older who received chemotherapy between 1991 and 2002. Of these, 15,346 (27%) received an erythropoiesis-stimulating agent. According to a report in the November 10th online issue of the Journal of the National Cancer Institute, the proportion of patients treated with erythropoietin or darbepoetin increased from 5% in 1991 to 45% in 2002. Despite this increase, the annual rate of blood transfusions was a constant 22% during the same time period, the report states. "Many of the patients in the study received both erythropoiesis-stimulating agents and blood transfusions over the course of their treatment," according to Dr. Dawn L. Hershman. J Natl Cancer Inst 2009.
N Z Med J. 2013 Nov 22. Pure red cell aplasia associated with recombinant erythropoietin: a case report and brief review of the literature. Pure red cell aplasia (PRCA) is a rare adverse effect of recombinant erythropoietin (rEPO). Affected patients rapidly become transfusion-dependent, with many requiring immunosuppressive therapy for remission. We report a confirmed case in an elderly female, possibly the first of its kind in New Zealand, who was started on rEPO for anaemia of chronic kidney disease. We also briefly review current literature on rEPO-associated PRCA.
Increased mortality with high doses in kidney patients
Use of controversial anemia drugs at high levels likely worsens heart problems and possibly chances for survival in kidney patients, according to a U.S. Medicare advisory panel in March 2010. Outside experts on the panel told the Centers for Medicare & Medicaid Services (CMS) that they were confident that use of the blockbuster drugs, called erythropoiesis-stimulating agents (ESAs), in chronic kidney disease patients could cause harm. In a series of votes, most panelists said there was enough data to draw those conclusions about increased heart risks. At the same time, evidence also showed ESAs could improve patients' quality of life and help them be active. At issue is whether changes are needed to address use of the drugs - Johnson & Johnson's Procrit and Amgen's Aranesp and Epogen. Concerns over possible heart risks and strong warnings for their use in cancer patients have already caused sales to slump as doctors scale back. Like cancer patients undergoing chemotherapy, those with kidney disease can also feel the fatigue and weakness of anemia. ESA drugs aim to boost red blood cells and improve energy. Doctors use them to prevent unnecessary blood transfusions that carry their own risks as patients await possible kidney transplantation. Current guidelines call for ESAs - synthetic forms of the erythropoietin hormone - to raise red blood cell levels to between 10 grams and 12 grams per deciliter, but recent studies linked higher doses to strokes, heart attacks or even death.
Erythropoietin anemia drug side effects and risks
The risks of anemia drugs known as erythropoiesis-stimulating agents, or ESAs are many. Studies show that patients with breast or advanced cervical cancers who receive erythropoiesis-stimulating agents to treat anemia caused by chemotherapy died sooner or have more rapid tumor growth than similar patients who don't receive the anemia drugs.
Long-term treatment with erythropoietin increases serum HDL-cholesterol levels in patients with chronic kidney disease.
Erythropoietin and hepatitis
Treatment with erythropoietin worsens thrombocytopenia induced by pegylated-interferon-alpha therapy in patients with chronic hepatitis C infection.